Mohamed A Osman, M.D., Hematopathology Fellow
Nam Ku, M.D., Assistant Clinical Professor UC Davis
Denis M. Dwyre, M.D., Professor UC Davis
Tonsillectomy, the surgical removal of tonsils, is one of the most frequent surgeries in the United States. Tonsil excision is usually performed to treat benign diseases such as sleep disordered breathing and recurrent pharyngitis. Typically in these situations, malignancy is an uncommon indication (1). Previous studies have shown occult lymphoid malignancy is rare in tonsillectomy specimens, and it has been argued that routine histologic evaluation is low-yield and not cost-effective for patients without worrisome clinical features (2). The incidence of lymphoma in tonsil specimens is even less frequent in pediatric patients. Lymphoma workup is frequently requested for routine tonsillectomy specimens, including pediatric cases. Here we will review literature and provide an indication and guideline for a cost-effective approach for selection of cases for lymphoma workup in pediatric patients.
Lymphoma Workup Protocol:
As discussed in our previous blog entry, a complete lymphoma workup consists of the following components (3):
- Histologic examination, including immunohistochemistry
- Flow cytometry
- Cytogenetics and molecular tests
The extensive work-up is performed because diagnosis of hematolymphoid neoplasms is often challenging and requires adequate immunophenotyping. Flow cytometry is commonly used in conjunction with histology and immunohistochemistry for this purpose. Although these tests are necessary for complete evaluation of lymphoproliferative disorder, they increase the overall cost and could become unnecessary financial burden for both patients and the Medical Center (4).
In this post we will review some published studies findings and our own ongoing study preliminary results, in an effort to come up with a cost-effective approach for tonsillectomy specimens work up.
A retrospective study performed here at UC Davis hospital in 2005 reviewed over 900 tonsillar specimens collected over five years at the medical center(5). There were a total 372 pediatric cases and 654 adult cases. Lymphoma workups were performed in 19 pediatric and 42 adult cases. No malignancy, including lymphoma, was detected in any pediatric cases. A total 90 of adult cases demonstrated neoplasm with squamous cell carcinoma being the most common diagnosis; eight cases of lymphoma were diagnosed (approximately 1.4%) in the adult cases. The cost of each lymphoma workup at that time (2005) was $4063 with Medicare reimbursement of $1180. They found that unilateral growth, rapidly enlarging tonsillar mass and grossly asymmetric tonsils as clinically worrisome features (5).
In an effort to improve the current practice, we are conducting a new study, in collaboration with our ENT colleagues, regarding lymphoma work-ups in tonsil specimens in pediatric patients. Preliminary data from this study shows similar findings. Out of 1451 pediatric (under 21 year of age) tonsil specimens received in our department from 1991 to 2018, only 3 cases were positive for lymphoproliferative diseases (approximately 0.2%). One of the three cases is from an HIV/AIDS patient.
A retrospective review of twenty studies found 54 malignancies from 54,901 patients (less than 0.1% prevalence), and most of the malignant cases (48 of 54; 88%) showed suspicious features such as asymmetry, cervical adenopathy, abnormal tonsil appearances, weight loss, or systemic symptoms (6). The study also evaluated the utility of flow cytometry in tonsillar specimens showing that hematolymphoid malignancy is uncommon, and flow cytometry was less accurate than histology / immunohistochemistry for the diagnosis (6).
Laboratory Best Practice:
As above studies demonstrated, lymphoma is an uncommon diagnosis in tonsillar specimen, especially in the general pediatric population. Thus, lymphoma work-up is generally not indicated for routine tonsillectomy cases. However, certain patients are at higher risk of having a hematolymphoid neoplasm involving the tonsil. These include patients with immunodeficiency (either primary or secondary such as transplant patients or HIV/AIDS) or strong family history indicating possible germline predispositions. Worrisome clinical features such as tonsillar asymmetry, rapid growth, cervical adenopathy, or B symptoms such as fever, night sweats or weight loss should also warrant a careful examination and possibly a lymphoma work-up.
Our proposed guidelines for lymphoma work-up request for tonsillar specimens:
- No lymphoma work-up indicated for pediatric patients without suspicious features listed above (histology only).
- Limited lymphoma work-up indicated for high-risk pediatric patients without any suspicious features (flow cytometry and/or immunostaining).
- Complete lymphoma workup indicated for any pediatric patients with high clinical suspicion
At the conclusion of the study, the goal is to develop consensus guidelines, in conjunction with ENT physicians.
- Aisagbonhi, Omonigho, et al. “Utility of Flow Cytometry in Diagnosing Hematologic Malignancy in Tonsillar Tissue.” International journal of surgical pathology5 (2017): 406-413.
- Chow W, Rotenberg BW. Discontinuing routine histopathological analysis after adult tonsillectomy for benign indication: routine histopathology of tonsil specimens. Laryngoscope. 2015;125:1595-1599.
- Osman, M., et al. “The Optimal Specimen for Lymphoma Workup”, UC Davis, 29, 2019, https://blog.ucdmc.ucdavis.edu/labbestpractice/index.php/2019/01/29/the-optimal-specimen-for-lymphoma-workup/
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Non-Hodgkin’s Lymphomas Version 3.2016. May 2016. https://www.nccn.org/professionals/physician_ gls/pdf/nhl.pdf. Accessed July 18, 2016.
- Yeung, Cecilia C., et al. “Evaluation of Tonsillectomy and Lymphoma Workup-Who Should Get a Lymphoma Workup? Is It Cost Effective?.” (2005): 3128-3128.
- Randall, David A., Peter J. Martin, and Lester DR Thompson. “Routine histologic examination is unnecessary for tonsillectomy or adenoidectomy.” The Laryngoscope 117.9 (2007): 1600-1604.